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Intrathecal injection of human placental mesenchymal stem cells derived exosomes significantly improves functional recovery in spinal cord injured rats

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Abstract

Background

Spinal cord injury (SCI) due to lack of restoration of damaged neuronal cells is associated with sensorimotor impairment. This study was focused on using the human placental mesenchymal stem cells- exosome (HPMSCs- Exosomes) in an animal model of severe SCI under myelogram procedure.

Methods and results

Intrathecal injection of exosomes was performed in the acute phase of SCI in female rats. The improved functional recovery of the animals was followed for 6 weeks in control (saline, n = 6) and HPMSCs- EXO (HPMSCs-Exosomes, n = 6) groups. Pathological changes and glial scar size were evaluated. The Immunohistochemistry (IHC) of GFAP and NF200 factors as well as the apoptosis assay was investigated in the tissue samples from the injury site. The results demonstrated that HPMSCs-exosomes can improve motor function by attenuating apoptosis of neurons at the injury site, decreasing GFAP expression and increasing NF200 in the HPMSCs-EXO group. Also, HPMSCs-exosomes by preventing the formation of cavities causes preservation of tissue in SCI rats.

Conclusions

These findings demonstrate the effectiveness of HPMSC-Exosomes as a therapeutic method to improve functional recovery, reduce pathological changes associated with injury, and prevent chronicity after SCI. The neuroprotective and anti-apoptotic potential of HPMSCs- Exosomes may be a promising therapeutic approach for SCI. Another result was the importance of intrathecal injection of exosomes in the acute phase, which accelerated the healing process. Furthermore, the myelogram can be a feasible and suitable method to confirm the accuracy of intrathecal injection and examine the subarachnoid space in the laboratory animals.

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Data availability

All data would be available on request.

Abbreviations

BBB:

Basso, beattie and bresnahan

FBS:

Fetal bovine serum

GFAP:

Glial fibrillary acidic protein

H&E:

Hematoxylin–eosin

hPMSCs:

Human mesenchymal stem cells

hPMSCs-exosomes:

Human placental mesenchymal stem cells derived exosome

IHC:

Immunohistochemistry

LP:

Lumbar puncture

MSC:

Mesenchymal stem cells

NF200:

Neurofilament 200

PFA:

Paraformaldehyde

PBS:

Phosphate buffered saline

SCI:

Spinal cord injury

TEM:

Transmission electron microscopy

TUNEL:

Terminal deoxynucleotidyl transferase-mediated dUTp nick end-labeling

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Acknowledgements

We are very grateful to everyone who contributed to the success of this research project.

Funding

This study was supported by the Clinical Biochemistry department of Tarbiat Modares University, Medical Sciences.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Post Office Box: 14115-111, Tehran, Iran

    Afsane Soleimani & Mohammad Javad Rasaee

  2. Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Post Office Box: 1983969411, Tehran, Iran

    Saeed Oraee Yazdani

  3. Department of Surgery & Radiology- Faculty of Veterinary Medicine, University of Tehran, Post Office Box: 14155-6619, Tehran, Iran

    Mirsepehr Pedram & Fatemeh Saadinam

  4. Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Post Office Box: 14115-111, Tehran, Iran

    Masoud Soleimani

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  1. Afsane Soleimani
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  3. Mirsepehr Pedram
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Contributions

AS: performed the experiments, analyzed data, and wrote the manuscript. SOY: discussed the results and analysis the data. MP: designed and made the animal model and the myelogram. FS: was a surgical assistant to create the animal model. MJR: designed research, discussed the results, edited this manuscript, and provided technical and material support. MS: designed the project and performed the development of methodology. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Mohammad Javad Rasaee or Masoud Soleimani.

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The authors declare that they have no conflict of interest.

Ethical approval

All animal operations were performed in accordance with the laboratory animal standards set by the Animal Ethics Committee of the Tarbiat Modares University of Medical Science (code of ethics: IR.MODARES.REC.1397.064).

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Soleimani, A., Oraee Yazdani, S., Pedram, M. et al. Intrathecal injection of human placental mesenchymal stem cells derived exosomes significantly improves functional recovery in spinal cord injured rats. Mol Biol Rep 51, 193 (2024). https://doi.org/10.1007/s11033-023-08972-7

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